VTechWorks staff will be away for the Thanksgiving holiday beginning at noon on Wednesday, November 27, through Friday, November 29. We will resume normal operations on Monday, December 2. Thank you for your patience.

Browsing by Author "Guevara, Christopher A."

Now showing 1 - 1 of 1
  • Thumbnail Image
    Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice
    de la Fuente Revenga, Mario; Zhu, Bohan; Guevara, Christopher A.; Naler, Lynette B.; Saunders, Justin M.; Zhou, Zirui; Toneatti, Rudy; Sierra, Salvador; Wolstenholme, Jennifer T.; Beardsley, Patrick M.; Huntley, George W.; Lu, Chang; González-Maso, Javier (Cell Press, 2021-10-19)
    Clinical evidence suggests that rapid and sustained antidepressant action can be attained with a single exposure to psychedelics. However, the biological substrates and key mediators of psychedelics’ enduring action remain unknown. Here, we show that a single administration of the psychedelic DOI produces fast-acting effects on frontal cortex dendritic spine structure and acceleration of fear extinction via the 5-HT2A receptor. Additionally, a single dose of DOI leads to changes in chromatin organization, particularly at enhancer regions of genes involved in synaptic assembly that stretch for days after the psychedelic exposure. These DOI-induced alterations in the neuronal epigenome overlap with genetic loci associated with schizophrenia, depression, and attention deficit hyperactivity disorder. Together, these data support that epigenomic-driven changes in synaptic plasticity sustain psychedelics’ long-lasting antidepressant action but also warn about potential substrate overlap with genetic risks for certain psychiatric conditions.